DESCRIPTION: Epidemiological studies have variously associated extremely low frequency (ELF) electromagnetic fields with leukemia, brain and breast cancer. Unfortunately, a rational scientific mechanism linking such fields with cancer is not known. Thus, one long-range goal is to establish a mechanistic link between ELF fields and cancer. Recently, we have shown the metabolic oscillations of human cells can resonate during migration or adherence in the presence of phase-matched ELF electric fields within the environmentally relevant intensity region. Environmental electromagnetic subharmonics that match metabolic oscillation frequencies could induce metabolic resonance thereby dramatically altering normal oscillatory metabolic reactions and, consequently, cell morphology and function (cell migration/invasive/adherence properties). To test if metabolic resonance provides a mechanistic link betwee ELF fields and cancer, we will expose tumor cells, leukemic cells, and control to electric fields during migration, adherence and invasive activities (models of cell detachment, invasion and metastasis). To control for the phase of metabolic oscillations, we will monitor NAD (P) H autofluorescence in (resonance) and phase-mismatched conditions. We will characterize the electric field intensity dependence of metabolic resonance. We will also examine cell morphology, cytoskeletal changes and pericellular proteolysis during metabolic resonance. Our electromechanical coupling hypothesis may be a physical mechanism linking weak fields to metabolic resonance and its downstream bioeffects. To test this primary coupling mechanism we will test the role of cell surface charges in metabolic resonance. Preliminary data show that high-amplitude NAD (P) H oscillations are associated with superoxide anion production. We will study the electric field intensity and phase-dependence of reactive oxygen metabolite production within leukocytes, tumor and leukemic cells. Using the comet and terminal deoxynucleotidyl transferase assays, we will link metabolic resonance/oxidant stress with DNA damage. A mechanistic series of events linking ELF fields with adherence/locomotion/invasive properties of cancer cells, metabolism and DNA damage will be identified; this may provide a physicochemical basis for ELF health effects.